In the last 10 years it has become generally accepted that asthma is an inflammatory disease of the airways. T lymphocytes play a key role in regulating this inflammatory response through the elaboration of cytokines such as IL-4, IL-5 and IFN-gamma. In this project we are examining the cytokine profiles of both peripheral blood and bronchoalveolar lavage (BAL) T cells from asthmatics and normal volunteers, using a novel technique to measure cytokine production at the single cell level. This technique has the advantage of allowing one to isolate cytokine production to specific subpopulations (CD4 and CD8) of T cells without the problematic physical purification of the cells. The initial phase of this work now in progress is designed to determine the frequency of Th1 and Th2 T cells in BAL and peripheral blood both before and after pulmonary allergen challenge. Initial results suggest that the dominant cells trafficking to the lung in asthmatic inflammation and the local production of cytokines with allergic effector function (IL-4 and IL-5) relate to specific subpopulations of T cells rather than the wholesale recruitment of Th 2 cells. In specific mouse models, NK 1.1 T cells rapidly produce IL-4 and IFN-gamma and are necessary for T cell priming and IgE production. We sought to demonstrate if similar cells could be detected in humans, and if so, would they have a similar link to IL-4 production. Using flow cytometry and PCR we have demonstrated analogous human cells bearing the Valpha24 T cell receptor. Unlike the murine cells, human Valpha24 T cells may predominately produce IFN-gamma.